Structure and Function of Paxillin
Paxillin 的结构和功能
基本信息
- 批准号:10396034
- 负责人:
- 金额:$ 40.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-07-01 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAdaptor Signaling ProteinAddressAnimal ModelApicalBiological ModelsBreast Epithelial CellsCell PolarityCellsCellular biologyCentrosomeCommunicationCytoskeletonDefectDepositionDevelopmentDiabetes MellitusDiseaseDisease ProgressionElementsEmbryonic DevelopmentEpithelialExtracellular MatrixF-ActinFocal AdhesionsFundingGoalsGolgi ApparatusHDAC6 geneHomeostasisIntermediate FilamentsInterventionKnockout MiceLightMalignant NeoplasmsMediator of activation proteinMesenchymalMicrotubulesMolecularMorphogenesisOrganoidsPlayPositioning AttributeProcessRegulationResearchResolutionRoleScaffolding ProteinSignal TransductionStructureTimeTissuesVimentincell motilitydevelopmental diseaseimaging approachknockout animalmigrationmouse modelnovelpaxillinpolarized cellprogramsreal-time imagestrafficking
项目摘要
PROJECT SUMMARY
The broad ongoing objective of this research program is to gain a deeper understanding of the
fundamental mechanisms by which the focal adhesion adaptor/scaffold proteins paxillin and Hic-5
contribute to cell-matrix signaling and thereby control of cell polarity and migration in development and
disease. Importantly, communication between the three elements of the cytoskeleton, the trafficking
machinery and cell-matrix interactions is essential for establishing both apical-basal and front-rear
migration polarity. However, our understanding of the key mechanisms coordinating and integrating
these processes remains incomplete. Through our development of new paxillin and Hic-5 knock out
mouse models, in combination with the use of various ex-vivo 1D, 2D and 3D cell matrix and organoid
model systems and real time imaging approaches, we have identified new roles for paxillin in
establishing epithelial and mesenchymal cell polarity, including regulation of centrosome and Golgi
organization and microtubule stability via control of HDAC6 activity. We have also identified Hic-5 as a
new mediator of F-actin-intermediate filament cross talk, mechanobiology and 3D extracellular matrix
deposition and remodeling. Using these model systems in conjunction with quantitative real time
confocal, light sheet and super resolution imaging approaches, the main goals that we will address in the
upcoming funding period are- Goal 1: How does paxillin contribute to the regulation of polarized
trafficking in directed mesenchymal cell migration? Goal 2: What is the role of paxillin in establishment of
apical-basal polarity and in branching morphogenesis in mammary epithelial cells and Goal 3: How does
Hic-5 regulate the vimentin intermediate filament cytoskeleton organization and function in motile cells
and during epithelial-mesenchymal transition? Through the elucidation of these mechanisms we will be
better positioned to develop rational approaches to disease intervention and to appreciate the basis of
developmental disorders.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Christopher E Turner其他文献
Christopher E Turner的其他文献
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{{ truncateString('Christopher E Turner', 18)}}的其他基金
Paxillin and Hic-5 in Coordination of Cancer Cell Invasion Mechanisms
Paxillin 和 Hic-5 协调癌细胞侵袭机制
- 批准号:
8216208 - 财政年份:2012
- 资助金额:
$ 40.5万 - 项目类别:
Paxillin and Hic-5 in Coordination of Cancer Cell Invasion Mechanisms
Paxillin 和 Hic-5 协调癌细胞侵袭机制
- 批准号:
8627588 - 财政年份:2012
- 资助金额:
$ 40.5万 - 项目类别:
Paxillin and Hic-5 in Coordination of Cancer Cell Invasion Mechanisms
Paxillin 和 Hic-5 协调癌细胞侵袭机制
- 批准号:
8462943 - 财政年份:2012
- 资助金额:
$ 40.5万 - 项目类别:
Paxillin and Hic-5 in Coordination of Cancer Cell Invasion Mechanisms
Paxillin 和 Hic-5 协调癌细胞侵袭机制
- 批准号:
8828598 - 财政年份:2012
- 资助金额:
$ 40.5万 - 项目类别:
ILK-Actopaxin Interactions in Cell Signaling
ILK-Actopaxin 在细胞信号转导中的相互作用
- 批准号:
7192947 - 财政年份:2007
- 资助金额:
$ 40.5万 - 项目类别:
ILK-Actopaxin Interactions in Cell Signaling
ILK-Actopaxin 在细胞信号转导中的相互作用
- 批准号:
7568280 - 财政年份:2007
- 资助金额:
$ 40.5万 - 项目类别:
ILK-Actopaxin Interactions in Cell Signaling
ILK-Actopaxin 在细胞信号转导中的相互作用
- 批准号:
7356055 - 财政年份:2007
- 资助金额:
$ 40.5万 - 项目类别:
ILK-Actopaxin Interactions in Cell Signaling
ILK-Actopaxin 在细胞信号转导中的相互作用
- 批准号:
7760145 - 财政年份:2007
- 资助金额:
$ 40.5万 - 项目类别: